Molecular Diagnostics
British Journal of Cancer (2008) 99, 314–320. doi:10.1038/sj.bjc.6604472 www.bjcancer.com
Published online 1 July 2008
Heterogeneity and clinical significance of ETV1 translocations in human prostate cancer
G Attard1,2,10, J Clark1,10, L Ambroisine3, I G Mills4, G Fisher3, P Flohr1, A Reid1,2, S Edwards1, G Kovacs5, D Berney6, C Foster7, C E Massie4, A Fletcher1, J S De Bono1,2, P Scardino8,9, J Cuzick3 and C S Cooper1 on behalf of the Transatlantic Prostate Group
- 1Institute of Cancer Research, Male Urological Cancer Research Centre, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
- 2The Royal Marsden NHS Trust Foundation Hospital, Downs, Road, Sutton, Surrey SM2 5PT, UK
- 3Department of Mathematics and Statistics, Cancer Research UK Centre for Epidemiology, Wolfson Institute of Preventive Medicine, St Bartholomew's Medical School, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK
- 4Department of Oncology, Uro-Oncology Research Group, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK
- 5Molekulare Onkologie, Heidelberg Klinikum, Ruprecht-Karls-Universitat, Im Neuenheimer Feld 365, Heidelberg 69120, Germany
- 6The Orchid Tissue Laboratory, St Bartholomew's Hospital, London EC1A 7BE, UK
- 7Department of Pathology, The University of Liverpool, Duncan Building, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, UK
- 8Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
- 9Department of Urology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
Correspondence: Dr J Clark, E-mail: jeremy.clark@icr.ac.uk
10Clark and Attard are joint first authors
Revised 12 May 2008; Accepted 20 May 2008; Published online 1 July 2008.
Abstract
A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer.
Keywords:
prostate cancer, ETV1, ACSL3, ACSL3:ETV1 fusion
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